Microbiology & Immunology Faculty
Molly Bergman, Ph.D.
The Bergman Lab focuses on host-pathogen interactions. We explore these interactions through the prism of host immune responses, with the idea that a clearer picture of immunity protects the reveals novel details of pathogenesis. To this end, we study two bacterial pathogens. Yersinia pseudotuberculosis provides an excellent model for studying localized and disseminated infection and ensuing mammalian immune responses; we seek to understand how host T cells recognize and eliminate bacterial pathogens like Yersinia, and correspondingly, how Yersinia evades immune recognition and clearance. Serratia marcescens is an opportunistic pathogen often associated with nosocomial outbreaks, and provides us with a probe to study virulence factors of “accidental” pathogens and the ensuing innate host responses in the lung. We study these two pathogens in three separate projects:
CD8+ T cell responses to an extracellular pathogen. We observed that CD8+ T cells protect hosts against Y. pseudotuberuclosis infection - a surprising finding, given that CD8+ T cells canonically target intracellular pathogens, while Yersinia spp. reside attached to the extracellular surface. We demonstrated a mechanism of protection: T cell-induced apoptosis marks Yersinia-associated host cells for ingestion by neighboring phagocytes, and thus indirectly clears the extracellular-attached bacteria. We are currently exploring the hypothesis that the host protein perforin, which T cells use to kill target cells, is critical for CD8+ T cell-mediated protection against Yersinia. Future work includes identification of natural Yersinia antigens stimulatory for T cells, in vivo antigen expression profiling, and exploration of how extraintestinial dissemination and localized tissue colonization influence T cell recognition in vivo.
The role of apoptosis during Yersinia infection. Apoptosis is a convergence point for our research. Our studies of Yersinia-specific CD8+ T cell responses indicated that T cell-induced host cell apoptosis limits Yersinia infection, leading to the hypothesis that apoptosis generally protects the host against bacteria. Yersinia spp. can also induce apoptosis-killing macrophages by injecting the pro-apoptotic protein YopJ. We are currently exploring the role that YopJ plays during dissemination and colonization in vivo.
Serratia marcescens virulence factors and respiratory innate immune responses. Studies of airway disease and infection are one strength of the UTHSCSA research community – to capitalize on this strength, and apply new genomic techniques to an emerging pathogen – we have obtained pilot funding to study acute pneumonia caused by S. marcescens. Current experiments are aimed at identifying novel virulence factors and characterizing the host response to lung infection.
Graduate students, in addition to technical staff and postdoctoral fellows, contribute significantly to the execution and success of Bergman Lab research. The successful graduate student in the Bergman Lab will apply a combination of acumen, curiosity and determination to studies of bacterial immunopathogenesis. Students will learn how to design hypothesis-driven experiments and perform molecular biology, genetics, cellular immunology and in vivo infectious disease techniques. Students will also master knowledge of the fields of microbial pathogenesis and immunology, and will travel to present research at national meetings. The motivated graduate student will find ample opportunities for exploration and success, and will be well prepared for a science career beyond graduate school.
- CD8+ T cells restrict Yersinia pseudotuberculosis infection: bypass of anti-phagocytosis by targeting antigen-presenting cells. Bergman MA, Loomis WP, Mecsas J, Starnbach MN, Isberg RR. PLoS Pathog. 2009 Sep;5(9):e1000573. Epub 2009 Sep 4.
- Yersinia pseudotuberculosis disseminates directly from a replicating bacterial pool in the intestine. Barnes PD, Bergman MA, Mecsas J, Isberg RR. J Exp Med. 2006 Jun 12;203(6):1591-601. Epub 2006 Jun 5.
- CD4+T-cell responses generated during murine Salmonella enterica serovar Typhimurium infection are directed towards multiple epitopes within the natural antigen FliC. Bergman MA, Cummings LA, Alaniz RC, Mayeda L, Fellnerova I, Cookson BT. Infect Immun. 2005 Nov;73(11):7226-35.
- CD4+ T-cells and toll-like receptors recognize Salmonella antigens expressed in bacterial surface organelles. Bergman MA, Cummings LA, Barrett SL, Smith KD, Lara JC, Aderem A, Cookson BT. Infect Immun. 2005 Mar;73(3):1350-6.
AffilliationsAmerican Society for Microbiology
American Association of Immunologists
Lab Rooms: STRF - 275.1 G-L Phone:(210) 562-4173
- Chris Mares Ph.D., Postdoctoral Fellow